The occurrence and frequency in human peripheral blood of variant lymphocytes that have lost HLA-A or B antigens is being determined as a measure of in vivo somatic cell mutation in man. Similar variant cells are being sought and induced in cultured human lymphoblastoid cells and permanent human T-cell lines maintained in culture with T-cell growth factors. The latter cells are being developed into a system for quantitative mutagenesis studies of several genetic markers in these functional human cells. HLA-B locus loss variants will be recovered from mutagenized populations of lymphoblastoid cells for study with the primed L-D typing (PLT) test and other means to detect HLA-D locus complete and partial loss variants. The former will be used as "hemozygous" priming cells in the PLT; and latter will be studies in an attempt to better understand the structure of this genetic region. T-cells are being propagated in vitro under conditions of selection in order to better characterize somatic cell variants arising in vivo for several genetic markers and to establish their heritability.